Pregnancy Outcomes After Exposure to Certolizumab Pegol: Updated Results From a Pharmacovigilance Safety Database

Abstract

Objective: Anti-tumor necrosis factor (anti-TNF) medications are effective in controlling chronic inflammatory diseases, but information about their use and safety in pregnancy is limited. Consequently, anti-TNF agents are often discontinued early in gestation. Certolizumab pegol (CZP), a PEGylated, Fc-free anti-TNF agent approved for the treatment of rheumatic diseases and/or Crohn's disease, has minimal to no active placental transfer. This analysis was undertaken to evaluate pregnancy outcomes in women receiving CZP, especially those exposed during early pregnancy.

Methods: Prospective and retrospective data on maternal CZP exposure were extracted from the UCB Pharma safety database through March 6, 2017. Analysis was limited to prospective reports to avoid potential bias associated with retrospective submissions. The numbers of live births, miscarriages, elective abortions, stillbirths, and major congenital malformations were ascertained.

Results: Of 1,137 prospectively reported pregnancies with maternal exposure to CZP, 528 (including 10 twin pregnancies) had 538 known outcomes: 459 live births (85.3%), 47 miscarriages (8.7%), 27 elective abortions (5.0%), and 5 stillbirths (0.9%). There were 8 major congenital malformations (1.7%) among the 459 infants. First trimester exposure occurred in 367 (81.2%) of 452 pregnancies resulting in 459 live births. Exposure during all 3 trimesters occurred in 201 (44.5%) of 452 pregnancies.

Conclusion: This analysis represents the largest cohort of pregnant women exposed to an anti-TNF agent for management of chronic inflammatory diseases. Analysis of pregnancy outcomes does not indicate a teratogenic effect of CZP, compared to the general population, nor an increased risk of fetal death. The data are reassuring for women of childbearing age considering treatment with CZP.

Figure 1

Overview of pregnancies exposed to certolizumab pegol (CZP). Eleven patients were included in more than 1 treatment indication category (rheumatic diseases, Crohn's disease, or other) due to multiple reported indications. RA = rheumatoid arthritis; AS = ankylosing spondylitis; axSpA = axial spondyloarthritis; PsA = psoriatic arthritis; JIA = juvenile idiopathic arthritis.

Figure 2

Known outcomes for prospectively reported pregnancies with maternal exposure to certolizumab pegol. Ten twin pregnancies are included in the total number of pregnancy outcomes (4 in mothers with rheumatic diseases, 5 in mothers with Crohn's disease [CD], and 1 in a mother with unknown indication). Miscarriage was defined as embryonic or fetal death before 20 weeks of gestation. Induced abortion includes both elective and medically indicated abortions.

Figure 3

Trimesters of maternal certolizumab pegol (CZP) exposure for prospectively reported pregnancies resulting in a live birth. A, Timing of CZP exposure for all pregnancies. A total of 452 pregnancies resulted in a live birth, including those in which the mother was exposed preconception (n = 5; CZP exposure stopped >14 days and ≤70 days prior to the first trimester) and pregnancies for which the timing of exposure could not be determined (n = 8), as well as 1 patient exposed in the first and third trimesters. Black, dark gray, and light gray shading represent CZP exposure during the first, second, and third trimesters, respectively; shading gradients reflect exposure during multiple trimesters. B, Exposure by indication for CZP use. There were 8 live births for which the timing of exposure could not be determined (n = 2 for patients with rheumatic disease and n = 6 for patients with Crohn's disease).